Pathogenetic mechanisms of calcium pyrophosphate dihydrate (CPPD) monosodium urate monohydrate (MSU) and hydroxyapatite (HA) crystal deposition diseases are being studied with the goal of developing means to prevent or treat the inflammatory and degenerative arthropathies that often accompany such deposition. Levels of inorganic pyrophosphate (PPi) in cultured skin fibroblasts from 2 families with multiple cases of CPPD crystal deposition disease will be compared with those of matched control subjects. The characteristics and pathogenetic significance of three (ecto) enzymatic activities found in intact living chondrocytes, a magnesium dependent, calcium inhibitible, inorganic pyrophosphatase, adenosine triphosphate (ATP) pyrophosphohydrolase and 5' nucleotidase will be studied. Attempts will be made to induce CPPD crystal formation in canine cartilage slices maintained in organ culture by generation of PPi from ATP added to the culture medium. The source of PPi released by cartilage in organ culture will be sought. The intracellular catabolism of CPPD and of hydroxyapatite (HA) crystals by cultured mammalian synovial cells will be studied in view of the augmented release of collagenase, neutral protease and prostaglandins (PG)E2 and F2Alpha that accompanies phagocytosis of these crystals. The cellular source of the secreted collagenase, the specificity of the increased collagenase synthesis induced by crystal endocytosis, and possible mitogenic effects of crystal endocytosis, will be studied. Data from these studies will be correlated with findings by gross pathologic examination and light and electron microscopic study of rabbit joints with synovial or cartilaginous HA calcification induced by vitamin D. The relationship of such calcification to degenerative changes in these joints will be explored. Additional studies of joint fluids from arthritis patients will be undertaken to extend our previous findings.